title: An indispensable role for the chemokine receptor CCR10 in IgA antibody-secreting cell accumulation.
abstract: The differential expression of chemokines and chemokine receptors, by tissues and leukocytes, respectively, contributes to the specific accumulation of leukocyte subsets to different tissues. CCR10/CCL28 interactions are thought to contribute to the accumulation of IgA Ab-secreting cells (ASC) to mucosal surfaces, such as the gastrointestinal tract and the lactating mammary gland. Although the role of CCL28 in lymphocyte homing is well established, direct in vivo evidence for CCR10 involvement in this process has not been previously shown. In this study, we describe the generation of a CCR10-deficient mouse model. Using this model, we demonstrate that CCR10 is critical for efficient localization and accumulation of IgA ASC to the lactating mammary gland. Surprisingly, IgA ASC accumulation to the gastrointestinal tract is minimally impacted in CCR10-deficient mice. These results provide the first direct evidence of CCR10 involvement in lymphocyte homing and accumulation in vivo, and demonstrate that reliance on CCR10-mediated recruitment of IgA ASC varies dramatically within mucosal tissues.
authors.affiliation: Perlmutter Laboratory and Department of Pediatrics, Children's Hospital, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Olivier
authors.initials: O
authors.lastname: Morteau
authors.forename: Craig
authors.initials: C
authors.lastname: Gerard
authors.forename: Bao
authors.initials: B
authors.lastname: Lu
authors.forename: Sorina
authors.initials: S
authors.lastname: Ghiran
authors.forename: Miriam
authors.initials: M
authors.lastname: Rits
authors.forename: Yuko
authors.initials: Y
authors.lastname: Fujiwara
authors.forename: Yuetching
authors.initials: Y
authors.lastname: Law
authors.forename: Kathryn
authors.initials: K
authors.lastname: Distelhorst
authors.forename: Elizabeth M
authors.initials: EM
authors.lastname: Nielsen
authors.forename: Erica D
authors.initials: ED
authors.lastname: Hill
authors.forename: Raymond
authors.initials: R
authors.lastname: Kwan
authors.forename: Nicole H
authors.initials: NH
authors.lastname: Lazarus
authors.forename: Eugene C
authors.initials: EC
authors.lastname: Butcher
authors.forename: Eric
authors.initials: E
authors.lastname: Wilson
mesh_terms: D000818:Animals; D000921:Antibody-Producing Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D002460:Cell Line; D002634:Chemotaxis, Leukocyte / Q000235:genetics / Q000276:immunology*; D007070:Immunoglobulin A / Q000096:biosynthesis / Q000378:metabolism*; D007420:Intestine, Large / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D007421:Intestine, Small / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D007774:Lactation / Q000276:immunology / Q000378:metabolism; D018655:Lymphocyte Count; D008321:Mammary Glands, Animal / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D054447:Receptors, CCR10 / Q000172:deficiency / Q000235:genetics / Q000502:physiology*
chemical_list: C515707:Ccr10 protein, mouse; D007070:Immunoglobulin A; D054447:Receptors, CCR10